Fused polycyclic compounds

ABSTRACT

The following fused polycyclic compound, analogues thereof or pharmaceutically acceptable salts thereof have an effect of increasing the sugar-transporting capacity and an effect of lowering the blood glucose level and, therefore, they are useful for preventing and/or treating diabetes and the like. 
                         
wherein R is a methoxy group, Y is a (2-thiazolyl)-2-ethylcarbonyl group, R 10  and R 13  are hydrogen atoms, and R 11  and R 12  are methyl groups.

CROSS REFERENCES TO RELATED APPLICATIONS

This application is a continuation of International Patent ApplicationNo. PCT/JP05/00348, filed on Jan. 14, 2005, and claims priority toJapanese Patent Application No. 2004-007179, filed on Jan. 14, 2004.

TECHNICAL FIELD OF THE INVENTION

The present invention relates to new fused polycyclic compounds anddrugs for treating diabetes which have the compounds as an activeingredient.

BACKGROUND OF THE INVENTION

Drug therapy of Type II diabetes is positioned as a treatment forpatients whose conditions are not sufficiently improved by dietarytherapy or exercise therapy. Up to now, agents have been developed suchas preparations with insulin that is an endogenous hormone controllinghypoglycemic actions, or oral hypoglycemic agents having actions such asinsulin secretagogue action or peripheral insulin sensitizing action. Atpresent, it is the mainstream method of drug therapy of Type II diabetesthat blood glucose is precisely controlled by using oral hypoglycemicagents. However, in case that sufficient, insulin actions cannot beobtained to improve hyperglycemia by using such agents, insulin therapyis applied as a main method. On the other hand, to Type I diabetes,administration of insulin therapy is the only treatment because suchpatients' insulin secretion ability is extinct.

Thus, though the insulin therapy is used as an important treatmentmethod, there are problems such as procedure complication and need ofpatient education because it is injection solutions. Accordingly,improvement in the administration method is strongly desired from theaspect of improvement in compliance. Recent years, several insulinadministration methods by various non-injection preparations to replaceinjection solutions have been developed and tried, but they are not ledto practical use because of the problems such as the poor absorptionefficiency and unstable absorption thereof.

As one of the main hypoglycemic actions of insulin, insulin has theaction which increases the sugar-transporting capacity of peripheralcells, makes sugars in the blood take in the peripheral cells, and, as aresult, lowers the blood glucose level. Thus, if new oral medicamentsare found such as those lowering the blood glucose level by an effect ofincreasing the sugar-transporting capacity of peripheral cells, it isexpected to become a promising treatment for diabetic diseases. Forexample, the compounds described in Patent Literature 1 are known.

[Patent Literature 1] WO 02/44180

DISCLOSURE OF THE INVENTION

The object of the present invention is to develop and provide a drug fortreating diabetes which has high medicinal properties and fewside-effects.

The further object of the present invention is to provide an agenthaving an effect of increasing the sugar-transporting capacity.

The additional object of the present invention is to provide ahypoglycemic agent.

The further additional object of the present invention is to provide adrug for preventing and/or treating diabetes, diabetic peripheralneuropathy, diabetic nephropathy, diabetic retinopathy, diabeticmacroangiopathy, impaired glucose tolerance or obesity.

The further additional object of the present invention is to provide anew fused polycyclic compound having a heterocyclic ring(s).

The further additional object of the present invention is to provide apharmaceutical composition.

The inventors thoroughly examined compounds useful as drugs for treatingdiabetes, which have a strong effect of increasing thesugar-transporting capacity, and found that specific fused polycycliccompounds have such effects. The present invention has been completedbased of this finding.

Namely, the present invention provides the following inventions.

(1) A fused polycyclic compound of the following formula (I) orpharmaceutically acceptable salts thereof:

wherein A represents an aromatic cyclic group, heterocyclic group oraliphatic cyclic group; R¹, R² and R³ may be same or different from eachother and each independently represent a hydrogen atom, halogen atom,hydroxyl group, mercapto group, alkoxy group, alkylthio group,alkylsulfonyl group, acyl group, acyloxy group, amino group, alkylaminogroup, carboxyl group, alkoxycarbonyl group, carbamoyl group, nitrogroup, cyano group, trifluoromethyl group, alkyl group which may have asubstituent(s), alkenyl group which may have a substituent(s), alkynylgroup which may have a substituent(s), aryl group which may have asubstituent(s), heteroaryl group which may have a substituent(s),benzyloxy group which may have a substituent(s), aryloxy group which mayhave a substituent(s), heteroaryloxy group which may have asubstituent(s), arylamino group which may have a substituent(s),arylvinyl group which may have a substituent(s) or arylethynyl groupwhich may have a substituent(s); —X— and —Z— may be same or differentfrom each other and each independently represent —O—, —NH—, —NR⁶—, —S—,—SO—, —SO₂—, —CH₂—, —CR⁴R⁵— or —CO—, wherein R⁶ represents a lower alkylgroup which may have a substituent(s), acyl group which may have asubstituent(s), alkoxycarbonyl group which may have a substituent(s),carbamoyl group which may have a substituent(s) or sulfonyl group whichmay have a substituent(s), R⁴ and R⁵ may be same or different from eachother and each independently represent a hydrogen atom, halogen atom,hydroxyl group, alkyl group, mercapto group, alkoxy group, alkylthiogroup, alkylsulfonyl group, acyl group, acyloxy group, amino group,alkylamino group, carboxyl group, alkoxycarbonyl group, carbamoyl group,nitro group, cyano group or trifluoromethyl group; —W— represents —NR⁹—,—O— or —CR⁷R⁸—, wherein R⁹ represents a hydrogen atom, lower alkyl groupwhich may have a substituent(s) or aryl group which may have asubstituent(s), R⁷ and R⁸ may be same or different from each other andeach independently represent a hydrogen atom, halogen atom, hydroxylgroup, alkyl group, mercapto group, alkoxy group, alkylthio group,alkylsulfonyl group, acyl group, acyloxy group, amino group, alkylaminogroup, carboxyl group, alkoxycarbonyl group, carbamoyl group, nitrogroup, cyano group or trifluoromethyl group; Y represents a lower alkylgroup which may have a substituent(s), acyl group which may have asubstituent(s), alkoxycarbonyl group which may have a substituent(s),carbamoyl group which may have a substituent(s) or sulfonyl group whichmay have a substituent(s); R¹⁰, R¹¹, R¹² and R¹³ may be same ordifferent from each other and each independently represent a hydrogenatom, halogen atom, lower alkyl group which may have a substituent(s),lower alkenyl group which may have a substituent(s), lower alkynyl groupwhich may have a substituent(s), aryl group which may have asubstituent(s), heteroaryl group which may have a substituent(s),carboxyl group, alkoxycarbonyl group, carbamoyl group or cyano group;and a, b and c represent a position of a carbon atom, respectively; withthe proviso that (i) the above substituent(s) is selected from the groupconsisting of a halogen atom, hydroxyl group, alkyl group, mercaptogroup, alkoxy group, alkylthio group, alkylsulfonyl group, acyl group,acyloxy group, amino group, alkylamino group, carboxyl group,alkoxycarbonyl group, carbamoyl group, nitro group, cyano group,trifluoromethyl group, aryl group and heteroaryl group; and(ii) two or more of R¹⁰, R¹¹, R¹² and R¹³ do not form a ring together.(2) The fused polycyclic compound or pharmaceutically acceptable saltsthereof according to above (1), wherein A represents an aromatic cyclicgroup or heterocyclic group; —X— represents —NH— or —NR⁶—; —Z—represents —CH₂— or —CR⁴R⁵—; —W— represents —NR⁹—; Y represents an acylgroup which may have a substituent(s), alkoxycarbonyl group which mayhave a substituent(s) or carbamoyl group which may have asubstituent(s); either one or both of R¹⁰ and R¹¹ is a hydrogen atom;and either one or both of R¹² and R¹³ is a hydrogen atom.(3) The fused polycyclic compound or pharmaceutically acceptable saltsthereof according to above (2), wherein Y is an acyl group which mayhave a substituent(s) and represented by the following formula (II):

wherein two carbon atoms in T may have a double bond or triple bond,part of the carbon atom(s) in the group may be substituted with anoxygen, sulfur or nitrogen atom, and T represents an alkylene grouphaving 1 to 7 carbon atoms; and C represents an aromatic cyclic group orheterocyclic group.(4) The fused polycyclic compound or pharmaceutically acceptable saltsthereof according to above (3), wherein C represents a furyl group whichmay have a substituent(s), thienyl group which may have asubstituent(s), oxazolyl group which may have a substituent(s),isoxazolyl group which may have a substituent(s), thiazolyl group whichmay have a substituent(s), oxadiazolyl group which may have asubstituent(s), thiadiazolyl group which may have a substituent(s),pyridyl group which may have a substituent(s), piperidyl group which mayhave a substituent(s), pyridonyl group which may have a substituent(s),pyridazinyl group which may have a substituent(s), pyrimidinyl groupwhich may have a substituent(s), imidazolyl group which may have asubstituent(s), or 4-oxothiazolidine-2-thionyl group which may have asubstituent(s); and -T- represents —CH₂— or —CH₂CH₂—.(5) The fused polycyclic compound or pharmaceutically acceptable saltsthereof according to above (4), wherein C represents a furyl group,thienyl group, oxazolyl group, isoxazolyl group, thiazolyl group,oxadiazolyl group, pyridyl group, piperidyl group, pyridazinyl group, orpyrimidinyl group.(6) The fused polycyclic compound or pharmaceutically acceptable saltsthereof according to above (2), wherein Y represents an unsubstitutedacyl group or acyl group which has an alkyl group(s) with 1 to 6 carbonatoms having a hydroxyl group as a substituent.(7) The fused polycyclic compound or pharmaceutically acceptable saltsthereof according to above (2), wherein A is a phenyl group substitutedupward on paper to Ring B; —X— represents —NH— or —NMe-; W is —NH—; bothR¹⁰ and R¹³ are hydrogen atoms; and R¹¹ and R¹² may be same or differentfrom each other and each independently represent a hydrogen atom, loweralkyl group which may have a substituent(s), lower alkenyl group whichmay have a substituent(s), or lower alkynyl group which may have asubstituent(s).(8) The fused polycyclic compound or pharmaceutically acceptable saltsthereof according to above (2), wherein all of R¹, R² and R³ arehydrogen atoms, or two in R¹, R² and R³ are hydrogen atoms and the restis an alkoxy group, alkylthio group, alkylsulfonyl group, acyl group,acyloxy group, amino group, alkylamino group, alkoxycarbonyl group,carbamoyl group, trifluoromethyl group, alkyl group which may have asubstituent(s), alkenyl group which may have a substituent(s), oralkynyl group which may have a substituent(s).(9) The fused polycyclic compound or pharmaceutically acceptable saltsthereof according to above (8), wherein all of R¹, R² and R³ arehydrogen atoms, or two in R¹, R² and R³ are hydrogen atoms and the restis an alkoxy group having 1 to 18 carbon atoms, alkylthio group having 1to 12 carbon atoms, alkylsulfonyl group having 1 to 12 carbon atoms,trifluoromethyl group, or alkyl group having 1 to 18 carbon atoms.(10) The fused polycyclic compound or pharmaceutically acceptable saltsthereof according to above (7), wherein R¹¹ and R¹² may be same ordifferent from each other and each independently represent a lower alkylgroup which may have a substituent(s), lower alkenyl group which mayhave a substituent(s), or lower alkynyl group which may have asubstituent(s).(11) The fused polycyclic compound or pharmaceutically acceptable saltsthereof according to above (10), wherein R¹¹ and R¹² may be same ordifferent from each other and each independently represent a lower alkylgroup which may have a substituent(s).(12) An agent for increasing the sugar-transporting capacity, whichcomprises the fused polycyclic compound or pharmaceutically acceptablesalts thereof according to any one of above (1) to (11) as an activeingredient.(13) A hypoglycemic agent; an agent for preventing and/or treatingdiabetes, diabetic peripheral neuropathy, diabetic nephropathy, diabeticretinopathy, diabetic macroangiopathy, impaired glucose tolerance, orobesity; or a pharmaceutical composition comprising the fused polycycliccompound or pharmaceutically acceptable salts thereof according to anyone of above (1) to (11) as an active ingredient.

BEST MODE FOR CARRYING OUT THE INVENTION

The effect of increasing the sugar-transporting capacity in the presentinvention indicates the action which increases the sugar-transportingcapacity via biological membranes. It may act on the sugartransportation from outside to inside of the biological membranes orthat from inside to outside of the biological membranes. Moreconcretely, for example, there is an insulin action, that is, the effectof increasing the glucose-transporting in and to adipose cells andmuscle cells.

Sugars in the “sugar-transporting” indicate pentoses or hexoses thatexist in vivo. Examples thereof include glucose, mannose, arabinose,galactose, and fructose. Glucose is preferable among them.

A lower alkyl group represents a linear- or branched-chain or cyclicalkyl group having 1 to 6 carbon atoms, preferably 1 to 4 carbon atomsand more preferably 1 to 3 carbon atoms. For example, it includes amethyl group, ethyl group, n-propyl group, n-butyl group, n-pentylgroup, n-hexyl group, isopropyl group, isobutyl group, sec-butyl group,tert-butyl group, isopentyl group, tert-pentyl group, neopentyl group,2-pentyl group, 3-pentyl group, n-hexyl group, 2-hexyl group,cyclopropyl group, cyclobutyl group, cyclopentyl group and cyclohexylgroup. A methyl group and ethyl group are preferable among them.

An aryl group represents a mono-, bi- or tri-cyclic aromaticsubstituent(s) composed of carbon atoms and preferably a mono- orbi-cyclic aromatic substituent(s) composed of 5 to 12 carbon atoms.Examples thereof are a phenyl group, indenyl group, naphthyl group andfluorenyl group, and a phenyl group is preferable among them.

A halogen atom includes a fluorine atom, chlorine atom, bromine atom andiodine atom.

An alkyl group represents a linear- or branched-chain or cyclic alkylgroup having 1 to 18 carbon atoms and preferably 1 to 12 carbon atoms.For example, it includes a methyl group, ethyl group, n-propyl group,n-butyl group, n-pentyl group, n-hexyl group, n-heptyl group, n-octylgroup, n-nonyl group, n-decyl group, n-undecyl group, n-dodecyl group,isopropyl group, isobutyl group, sec-butyl group, tert-butyl group,isopentyl group, tert-pentyl group, neopentyl group, 2-pentyl group,3-pentyl group, n-hexyl group, 2-hexyl group, tert-octyl group,cyclopropyl group, cyclobutyl group, cyclopentyl group, cyclohexyl groupand 1-adamantyl group. An n-hexyl group, n-heptyl group, n-octyl group,n-nonyl group, n-decyl group, n-undecyl group, n-dodecyl group,isopropyl group, isobutyl group, sec-butyl group, tert-butyl group,isopentyl group, tert-pentyl group, neopentyl group, 2-pentyl group,3-pentyl group, n-hexyl group, 2-hexyl group, tert-octyl group,cyclopropyl group, cyclobutyl group, cyclopentyl group, cyclohexylgroup, 1-adamantyl group and the like are preferable, and an isopropylgroup, tert-butyl group, tert-octyl group, 1-adamantyl group and thelike are more preferable among them. Further, a lower alkyl group isalso preferable.

An alkenyl group and alkynyl group include those having 2 to 18 carbonatoms, preferably 2 to 12 carbon atoms and more preferably 2 to 6 carbonatoms.

An alkoxy group represents an alkoxy group which has a linear- orbranched-chain or cyclic alkyl group having 1 to 18 carbon atoms,preferably 1 to 12 carbon atoms and more preferably 1 to 6 carbon atoms.For example, it includes a methoxy group, ethoxy group, n-propoxy group,n-butoxy group, n-pentyloxy group, n-hexyloxy group, n-heptyloxy group,n-octyloxy group, n-nonyloxy group, n-decyloxy group, n-undecyloxygroup, n-dodecyloxy group, isopropoxy group, isobutoxy group, sec-butoxygroup, tert-butoxy group, cyclopropyloxy group, cyclobutoxy group,cyclopentyloxy group, cyclohexyloxy group, cycloheptyloxy group,2-cyclohexylethoxy group, 1-adamantyloxy group, 2-adamantyloxy group,1-adamantylmethyloxy group, 2-(1-adamantyl)ethyloxy group andtrifluoromethoxy group. Among them, a methoxy group, ethoxy group,n-propoxy group, isopropoxy group, n-butoxy group, tert-butoxy group,n-pentyloxy group and n-hexyloxy group are preferable.

Further the alkoxy group includes the alkoxy group substituted with afluorine atom(s). More concretely, it includes a fluoromethyloxy group,trifluoromethyloxy group, trifluoroethyloxy group, andpentafluoroethyloxy group. A trifluoromethyloxy group is preferableamong them.

An alkylthio group represents an alkylthio group which has a linear- orbranched-chain or cyclic alkyl group having 1 to 12 carbon atoms andpreferably 1 to 6 carbon atoms. For example, it includes a methylthiogroup, ethylthio group, n-propylthio group, isopropylthio group,n-butylthio group, isobutylthio group, sec-butylthio group,tert-butylthio group, cyclopropylthio group, cyclobutylthio group,cyclopentylthio group and cyclobutylthio group.

An alkylsulfonyl group represents an alkylsulfonyl group which has alinear- or branched-chain or cyclic alkyl group having 1 to 12 carbonatoms and preferably 1 to 6 carbon atoms. For example, it includes amethanesulfonyl group, ethanesulfonyl group, propanesulfonyl group,butanesulfonyl group, pentanesulfonyl group, hexanesulfonyl group,heptanesulfonyl group, octanesulfonyl group, nonanesulfonyl group,decanesulfonyl group, undecanesulfonyl group and dodecanesulfonyl group.

An acyl group represents a formyl group, an acyl group which has alinear- or branched-chain or cyclic alkyl group having 1 to 6 carbonatoms and preferably 1 to 4 carbon atoms, an acyl group which has alinear- or branched-chain or cyclic alkenyl group having 1 to 6 carbonatoms and preferably 1 to 4 carbon atoms, an acyl group which has alinear- or branched-chain or cyclic alkynyl group having 1 to 6 carbonatoms, or an acyl group which has an aryl group that may be substituted.Examples thereof are a formyl group, acetyl group, propionyl group,butyryl group, isobutyryl group, valeryl group, isovaleryl group,pivaloyl group, hexanoyl group, acryloyl group, metacryloyl group,crotonoyl group, isocrotonoyl group, benzoyl group and naphthoyl group.Further, it also includes the acyl group which may have asubstituent(s), indicated as the above formula (II). The alkyl group inthe acyl group may have a hydroxy group or halogen group.

An acyloxy group represents a formyloxy group, an acyloxy group whichhas a linear- or branched-chain or cyclic alkyl group having 1 to 6carbon atoms, or an acyloxy group which has an aryl group that may besubstituted. For example, it includes a formyloxy group, acetyloxygroup, propionyloxy group, butyryloxy group, isobutyryloxy group,valeryloxy group, isovaleryloxy group, pivaloyloxy group, hexanoyloxygroup, acryloyloxy group, metacryloyloxy group, crotonoyloxy group,isocrotonoyloxy group, benzoyloxy group and naphthoyloxy group.

Further, the acyloxy group also includes the oxy group substituted withan acyl group(s) which may have a substituent(s), indicated as the aboveformula (II).

An alkylamino group represents an amino group which is monosubstitutedor disubstituted with an alkyl group(s), and examples of the alkylgroup(s) are the same as those mentioned in the above “alkyl group.”Concretely, they include a methylamino group, ethylamino group,propylamino group, isopropylamino group, dimethylamino group,diethylamino group, dipropylamino group, diisopropylamino group andmethylethylamino group.

An alkoxycarbonyl group represents an alkoxycarbonyl group which has alinear- or branched-chain or cyclic alkyl group having 1 to 8 carbonatoms. Examples thereof are a methoxycarbonyl group, ethoxycarbonylgroup, propoxycarbonyl group, isopropoxycarbonyl group, n-butoxycarbonylgroup, isobutoxycarbonyl group, sec-butoxycarbonyl group,tert-butoxycarbonyl group and benzyloxycarbonyl group.

A carbamoyl group represents a carbamoyl group which may have a linear-or branched-chain or cyclic alkyl group having 1 to 6 carbon atoms on anitrogen. For example, it includes a carbamoyl group, N-methylcarbamoylgroup, N-ethylcarbamoyl group, N,N-dimethylcarbamoyl group,N-pyrrolidylcarbonyl group, N-piperidylcarbonyl group andN-morpholinylcarbonyl group.

A sulfonyl group represents a sulfonyl group which may have a linear- orbranched-chain or cyclic alkyl group having 1 to 6 carbon atoms on asulfur atom. For example, it includes a methylsulfonyl group,ethylsulfonyl group, propylsulfonyl group and butylsulfonyl group.

An aromatic ring represents a mono-, bi- or tri-cyclic aromatic ringcomposed of carbon atoms and preferably a monocyclic or bicyclicaromatic ring. For example, it includes a benzene ring, naphthalenering, indene ring and fluorene ring, and a benzene ring and naphthalenering are preferable.

A heterocyclic ring represents a heterocyclic ring consisting of 1 to 3ring(s) each comprising 5 to 7 members of carbon and nitrogen, oxygen,sulfur or the like. For example, it includes a pyridine ring,dihydropyran ring, pyridazine ring, pyrimidine ring, pyrazine ring,pyrrole ring, furan ring, thiophene ring, oxazole ring, isooxazole ring,pyrazole ring, imidazole ring, thiazole ring, isothiazole ring,thiadiazole ring, pyrrolidine ring, piperidine ring, piperazine ring,indole ring, isoindole ring, benzofuran ring, isobenzofuran ring,benzothiophene ring, benzopyrazole ring, benzoimidazole ring,benzooxazole ring, benzothiazole ring, purine ring, pyrazolopyridinering, quinoline ring, isoquinoline ring, naphthyridine ring, quinazolinering, benzodiazepine ring, carbazole ring and dibenzofuran ring. Apyridine ring, pyrimidine ring, pyridazine ring, pyrimidine ring, furanring and thiophene ring are preferable among them.

An aliphatic ring represents a monocyclic or bicyclic aliphatic ringwhich is composed of carbon atoms. For example, it includes acyclopropane ring, cyclobutane ring, cyclopentane ring, cyclohexanering, cycloheptane ring, cyclooctane ring, decalin rings and norbornanering, and cyclohexane ring is preferable. It preferably has 3 to 8carbon atoms.

An heteroaryl group represents an aromatic heterocyclic substituentconsisting of 1 to 3 ring(s) each comprising 5 to 7 members of carbonand nitrogen, oxygen, sulfur or the like. For example, it includes apyridyl group, pyridazinyl group, pyrimidinyl group, pyrazinyl group,pyrrolyl group, furanyl group, thienyl group, oxazolyl group, isoxazolylgroup, pyrazolyl group, imidazolyl group, thiazolyl group, isothiazolylgroup, thiadiazolyl group, indolyl group, isoindolyl group, benzofurylgroup, isobenzofuryl group, benzothienyl group, benzopyrazolyl group,benzoimidazolyl group, benzoxazolyl group, benzothiazolyl group,quinolyl group, isoquinolyl group, naphthyridinyl group and quinazolylgroup. A 2-pyridyl group, 3-pyridyl group, 4-pyridyl group and1-pyrazolyl group are preferable among them.

An aryloxy group is an aryloxy group having an aryl group on an oxygenatom, and examples of the aryl group are the same as those mentioned inthe above “aryl group.” Concretely, it includes a phenoxy group,1-naphthyloxy group and 2-naphthyloxy group.

A heteroaryloxy group is a heteroaryloxy group having a heteroaryl groupon an oxygen atom, and examples of the heteroaryl group are the same asthose mentioned in the above “heteroaryl group.” Concretely, it includesa 2-pyridyloxy group, 3-pyridyloxy group, 4-pyridyloxy group and2-pyrimidinyloxy group.

An arylamino group is an arylamino group having an aryl group(s) on anitrogen atom and examples of the aryl group(s) are the same as thosementioned in the above “aryl group.” Concretely, it includes aphenylamino group, 1-naphthylamino group and 2-naphthylamino group.

An arylvinyl group is a vinyl group of which the first position or thesecond position is substituted with an aryl group(s), and examples ofthe aryl group(s) are the same as those mentioned in the above “arylgroup.” Concretely, it includes a 1-phenylvinyl group and 2-phenylvinylgroup.

An arylethynyl group is an ethynyl group of which the second position issubstituted with an aryl group(s), and examples of the aryl group(s) arethe same as those mentioned in the above “aryl group.” Concretely, itincludes a phenylethynyl group.

The term “which may have a substituent(s)” includes both cases in whicha group does not have any substituents and in which a group has asubstituent(s). In case that a group has a substituent(s), at least oneor more thereof are substituted with the substituent(s) mentioned in theabove (I). The substituent(s) may be same or different from each other,and the position and number thereof are optional and not particularlylimited.

Further, in the present invention, the fused polycyclic compound of theformula (I) according to claim 1 or pharmaceutically acceptable saltsthereof are preferably those mentioned below.

R¹, R² and R³ are preferably a hydrogen atom, halogen atom, hydroxylgroup, alkyl group, alkoxy group, alkylthio group, acyl group, acyloxygroup, amino group, alkoxycarbonyl group, carbamoyl group, nitro group,cyano group, trifluoromethyl group, trifluoromethoxy group, aryl groupwhich may have a substituent(s), heteroaryl group which may have asubstituent(s), benzyloxy group, aryloxy group which may have asubstituent(s) or arylethynyl group which may have a substituent(s).More preferable ones are a hydrogen atom, halogen atom, hydroxyl group,methyl group, ethyl group, propyl group, isopropyl group, cyclopropylgroup, methoxy group, ethoxy group, methylthio group, ethylthio group,n-propoxy group, isopropoxy group, trifluoromethyl group andtrifluoromethoxy group.

—X— is preferably —NH—, —NR⁶— wherein R⁶ represents a lower alkyl group,—O—, —S— or —CH₂—. —NH— or —NMe- is more preferable among them. —NH— isparticularly preferable among them.

—Y— is preferably an acyl group which may have a substituent(s),alkoxycarbonyl group which may have a substituent(s), or carbamoyl groupwhich may have a substituent(s). More preferable ones are an acetylgroup, propanoyl group, butanoyl group, hydroxyacetyl group,methoxycarbonyl group, ethoxycarbonyl group, ethylcarbamoyl group andthe acyl group of the formula (II). Besides, an acetyl group, propanoylgroup, hydroxyacetyl group, 3-(2-thiazolyl)propanoyl group, or3-(2-pyridyl)propanoyl group is further more preferable.

—Z— is preferably —NH— or —CR⁴R⁵— wherein R⁴ and R⁵ may be same ordifferent from each other and each independently represent a hydrogenatom or a lower alkyl group which may have a substituent(s), and —CH₂—is more preferable.

—W— is preferably —NH—, —NR⁹— wherein R⁹ represents a lower alkyl group,or —CH₂—, and —NH— is more preferable.

A is preferably an aromatic cyclic group or a heterocyclic group. Abenzene ring, pyridine ring, pyrimidine ring, and thiophene ring aremore preferable, and a benzene ring is further more preferable.

As for the configuration of a carbon atom in the position c, it ispreferable that A is substituted upward or downward on paper to B, andit is more preferable that A is substituted upward on paper to B.

Ring C is preferably a furan which may have a substituent(s), thiophenewhich may have a substituent(s), oxazole which may have asubstituent(s), isoxazole which may have a substituent(s), thiazolewhich may have a substituent(s), oxadiazole which may have asubstituent(s), thiadiazole which may have a substituent(s), pyridinewhich may have a substituent(s), piperidine which may have asubstituent(s), pyridone which may have a substituent(s), pyridazinewhich may have a substituent(s), pyrimidine which may have asubstituent(s), imidazole which may have a substituent(s), or4-oxothiazolidine-2-thione which may have a substituent(s). A pyridinewhich may have a substituent(s) or thiadiazole which may have asubstituent(s) are more preferable among them. Particularly, thiazoleand pyridine are more preferable.

-T- is preferably a bond consisting of one or two atom(s). —CH₂— or—CH₂CH₂— is more preferable, and —CH₂CH₂— is particularly preferable.

R¹⁰, R¹¹, R¹² and R¹³ may be same or different from each other andpreferably each independently represent a hydrogen atom, lower alkylgroup which may have a substituent(s), alkynyl group which may have asubstituent(s), or alkenyl group which may have a substituent(s). It isfurther more preferable that R¹⁰ and R¹³ are hydrogen atoms, and R¹¹ andR¹² may be same or different from each other and each independentlyrepresent a hydrogen atom, methyl group, ethyl group, n-propyl group,isopropyl group, cyclopropyl group, monofluoromethyl group,monofluoroethyl group, or trifluoromethyl group.

It is particularly preferable that R¹⁰ and R¹³ are hydrogen atoms.

It is particularly preferable that R¹¹ and R¹² are methyl groups orethyl groups.

The pharmaceutically acceptable salts include, for example, in the caseof the compounds of the present invention, which are sufficientlyacidic, ammonium salts thereof, alkali metal salts (such as sodium saltsand potassium salts, as preferable examples), alkaline earth metal salts(such as calcium salts and magnesium salts, as preferable examples); assalts of an organic base, for example, dicyclohexylamine salts,benzathine salts, N-methyl-D-glucan salts, hydramine salts, and salts ofamino acids such as arginine and lysine. Further, in the case of thecompounds of the present invention, which are sufficiently basic, thesalts include acid addition salts thereof, such as those with inorganicacids, e.g. hydrochloric acid, sulfuric acid, nitric acid and phosphoricacid; or those with organic acids, e.g. acetic acid, lactic acid, citricacid, tartaric acid, maleic acid, fumaric acid and monomethyl sulfate.In some cases, they may be wet salts or hydrates.

The present invention includes all isomers such as optical isomers andgeometric isomers, hydrates, solvates or crystal forms.

The compound of the present invention can be synthesized by using orapplying the method described in WO02/44180.

For example, in the compound (I) of the present invention, a compound(IX) wherein —Z— is —CH₂—; and —X— and —W— are —NH— can be synthesizedas mentioned below. Namely, a diamine (III) and a compound (IV) arefused to form a compound (V); and then the compound (V) is fused with analdehyde (VI) to form a compound (VII). The compound (VII) is led to acompound (VIII) by alkylation or acylation in accordance with knownmethods. In case that R¹⁴ is not hydrogen, the lactam part thereof isdeprotected to be able to obtain a compound (IX).

Further, in the compound (I) of the present invention, a compound (XI)wherein —Z— is —CH₂—; —W— is —NH—; and —X— is —NR⁶— wherein R⁶ is analkyl group which may have a substituent(s) can be synthesized asmentioned below. Namely, an alkylating agent such as alkyl halide isacted on the compound (VIII) under the existence of a base such assodium hydride to form a compound (X). Then, the lactam part thereof isdeprotected to be able to obtain a compound (XI).

As the diamine (III) used as a raw ingredient, known diamines can beused without change, or those synthesized by the method described in aliterature (Tetrahedron Asynmetry 1991, 2(10), 981-982) or those easilyled from known diols and dicarboxylic derivatives by the known methodscan be used. The compound (IV) can be synthesized by the methoddescribed in a literature (Tetrahedron Asynmetry 1996, 7(8), 2365-2370)or that described in WO02/44180.

The compounds of the present invention other than those mentioned abovecan also be synthesized by applying the above reactions.

Meanwhile, the compounds of the present invention obtained by the abovemethods can be purified with methods usually used in organic syntheses,such as extraction, distillation, crystallization and columnchromatography.

The obtained compounds of the present invention have an effect ofincreasing the sugar-transporting capacity as mentioned below, and areuseful for treating patients, taking advantage of this action. Namely,since an effect of increasing the sugar-transporting capacity lowers theblood glucose level, the compounds of the present invention are usefulas drugs preventing and/or treating diabetes, diabetic peripheralneuropathy, diabetic nephropathy, diabetic retinopathy, diabeticmacroangiopathy, impaired glucose tolerance or obesity.

When using the compounds of the present invention as the drugspreventing and/or treating diabetes, diabetic peripheral neuropathy,diabetic nephropathy, diabetic retinopathy, diabetic macroangiopathy,impaired glucose tolerance or obesity, they can be administered orally,intravenously, or transdermally. Though the dosage differs depending ona patient's symptom, age and administration method, it is usually 0.001to 1000 mg/kg/day.

The compounds of the present invention can be formulated into apharmaceutical preparation by ordinary methods. The dosage forms are,for example, injection solvents, tablets, granules, subtle granules,powders, capsules, cream pharmaceuticals and suppositories. Thepreparation carriers include such as lactose, glucose, D-mannitol,starch, crystalline cellulose, calcium carbonate, kaolin, starch,gelatin, hydroxypropyl cellulose, hydroxypropyl methyl cellulose,polyvinylpyrrolidone, ethanol, carboxy methyl cellulose, carboxy methylcellulose calcium salts, magnesium stearate, talc, acetyl cellulose,sucrose, titanium oxide, benzoic acid, p-hydroxybenzoate ester, sodiumdehydroacetate, gum arabic, tragacanth, methyl cellulose, egg yolk,surfactants, sucrose, simple syrup, citric acid, distilled water,ethanol, glycerin, propylene glycols, macrogol, monobasic sodiumphosphate, dibasic sodium phosphate, sodium phosphate, glucose, sodiumchloride, phenol, thimerosal, p-hydroxybenzoate ester and acid sodiumsulfite. They are used by being mixed with the compounds of the presentinvention depending on the dosage forms.

Further, the content of the active ingredient of the present inventionin the preparation of the present invention significantly variesdepending on the dosage forms and is not particularly limited.Generally, the content is about 0.01 to 100 wt %, and preferably 1 to100 wt % to a total amount of compositions.

The compounds of the present invention have an effect of increasing thesugar-transporting capacity, and are useful for treating the diabeticdiseases. Namely, since an effect of increasing the sugar-transportingcapacity lowers the blood glucose, the compounds of the presentinvention are useful as drugs preventing and/or treating diabetes,diabetic peripheral neuropathy, diabetic nephropathy, diabeticretinopathy, diabetic macroangiopathy, impaired glucose tolerance orobesity.

Next, Examples will further illustrate the present invention. They onlyexplain the present invention and do not particularly limit theinvention.

Example 1

464 mg (5.27 mmol) of (R,R)-2,3-diaminobutan (IIIa) and 1.23 g (5.27mmol) of a compound (IVa) synthesized by the method described in aliterature (Tetrahedron Asynmetry 1996, 7(8), 2365-2370) were fused andpurified in accordance with the method described in WO02/44180 to obtain1.00 g of a Process 1 compound (Va) (yield 63%) as a pale yellow solidsubstance.

1H-NMR (300 MHz, CDCl3) δ=1.07 (3H, d, J=6.3 Hz), 1.14 (3H, d, J=6.6Hz), 2.97-3.17 (2H, m), 4.21 (1H, d, J=18.0 Hz), 4.27 (1H, d, J=18.0Hz), 4.67 (1H, s), 5.24 (2H, s), 5.82 (1H, d, J=7.5 Hz), 7.25-7.44 (5H,m). MS(ESI) m/z 304 (M+H)+.

441 mg (1.46 mmol) of the Process 1 compound (Va) and 218 mg (1.60 mmol)of o-anisaldehyde were fused and purified in accordance with the methoddescribed in WO02/44180 to obtain 426 mg of a Process 2 compound (VIIa)(yield 69%)

1H-NMR (300 MHz, CDCl3) δ=0.86 (3H, d, J=6.6 Hz), 1.05 (3H, d, J=6.6Hz), 2.43-2.56 (1H, m), 3.22-3.36 (1H, m), 3.86 (3H, s), 4.21 (1H, d,J=18.0 Hz), 4.28 (1H, d, J=18.0 Hz), 4.55 (1H, s), 5.33 (1H, d, J=13.5Hz), 5.39 (1H, d, J=13.5 Hz), 6.78-6.93 (3H, m), 7.16-7.45 (7H, m).MS(ESI) m/z 422 (M+H)+.

(Process 3)

0.2 mL of acetic anhydride was added to a solution consisting of 64 mg(0.152 mmol) of the Process 2 compound (VIIa) and 2 mL of pyridine andstirred for 15 hours. The reaction solution was condensed under reducedpressure and separated by the ordinary separation treatment. Then, theorganic layer thereof was dried on anhydrous sodium sulfate andcondensed under reduced pressure. The obtained oily substance wasdissolved in methanol, and the catalytic reduction with hydrogen wasconducted thereto with 10% palladium carbon under normal pressure. Then,the reaction substance was purified by silica gel column chromatographyto obtain a compound 1.

The structural formula of the compound 1 and data on the compound areshown in the following Table 1. In this regard, the symbols in the Tableare as follows: No.: Example/Compound No., R: a substituent on a benzenering, D: data on the compound, MS:ESI-MS m/z, N1: 1H-NMR (DMSO-d6, TMSinternal standard, δ ppm). The number located in front of a substituentin R indicates the position of the substituent on a benzene ring.

Examples 2 to 15

Compounds 2 to 15 shown in the following Table 1 were synthesized by thesame method as that of Example 1.

Meanwhile, (R,R)-3,4-diaminohexane used in Examples 14 and 15 wasobtained by diaminating (S,S)-3,4-dihydroxyhexane (such as TetrahedronLetters, 1991, 32, 883) in accordance with the amination methoddescribed in a literature (Tetrahedron Asymmetry, 1999, 10, 3559).

TABLE 1 (XII)

No. R —Y R¹⁰ R¹¹ R¹² R¹³ D 1 2-OMe

H Me Me H N1: 0.95(3H, d, J=6.9 Hz), 0.96(3H, d, J=6.0 Hz), 2.13(3H, s),2.86-2.98(1H, m), 3.75(1H, d, J=16.5 Hz), 3.83(3H, s), 3.84(1H, d,J=16.5 Hz), 3.91-4.03(1H, m), 5.70(1H, s), 6.61(1H, s), 6.78(1H, s),6.83-7.06(3H, m), 7.23-7.31(1H, m). MS: 330(M+H)+ 2 2-OMe

H Me Me H N1: 0.99(3H, d, J=6.0 Hz), 1.02(3H, d, J=6.0 Hz),2.92-3.04(1H, m), 3.76(1H, d, 15 Hz), 3.81(3H, s), 3.84(1H, d, 15.0 Hz),3.86-4.01(2H, m), 4.28(1H, t, J=6.0 Hz), 4.48(1H, dd, J=15.0&6.0 Hz),5.46(1H, s), 6.69(1H, s), 6.82(1H, s), 6.85-7.06(3H, m), 7.25-7.33(1H,m). MS: 346(M+H)+ 3 2-OMe

H Me Me H N1: 0.92-1.04(9H, m), 2.24-2.40(1H, m), 2.59-2.74(1H, m),2.87-3.01(1H, m), 3.75(1H, d, 16.0 Hz), 3.83(1H, d, 16.0 Hz),3.91-4.03(1H, m), 5.78(1H, s), 6.59(1H, s), 6.77(1H, s), 6.82-7.05(3H,m), 7.23-7.31(1H, m). MS: 344(M+H)+ 4 2-SMe

H Me Me H N1: 0.94(3H, d, J=6.0 Hz), 1.04(3H, d, J=6.9 Hz), 2.19(3H, s),2.51(3H, s), 3.78(1H, d, J=16.0 Hz), 3.88(1H, d, J=16.0 Hz),3.90-4.03(1H, m), 5.45(1H, s), 6.66(1H, s), 6.84(1H, s), 6.96-7.01(1H,m), 7.08-7.15(1H, m), 7.27-7.41(2H, m). MS: 346(M+H)+ 5 2-SMe

H Me Me H N1: 0.97(3H, d, J=6.3 Hz), 1.11(3H, d, J=7.2 Hz), 2.51(3H, s),2.74-2.88(1H, m), 3.71-4.01(4H, m), 4.40(1H, t, J=6.0 Hz), 4.78(1H, dd,J=15.6&5.4 Hz), 5.32(1H, s), 6.74(1H, s), 6.89(1H, s), 6.96-7.18(2H, m),7.29-7.41(2H, m). MS: 362(M+H)+ 6 2-cyclo propyl

H Me Me H N1: 0.55-1.05(4H, m), 0.99(3H, d, J=6.6 Hz), 1.10(3H, d, J=6.6Hz), 1.95-2.02(1H, m), 2.90-3.05(1H m), 3.78(1H, d, J=16.5 Hz),3.80-3.90(1H, m), 3.89(1H, d, J=16.5 Hz), 3.95-4.05(1H, m),4.40-4.55(2H, m), 5.68(1H, s), 6.69(1H, s), 6.88(1H, s), 6.96-7.26(4H,m). MS: 356(M+H)+ 7 2-OMe

H Me Me H N1: 0.99(6H, d, J=6.9 Hz), 2.68-3.37(5H, m), 3.76(3H, s),3.77(1H, d, J=16.0 Hz), 3.86(1H, d, J=16.0 Hz), 3.92-4.05(1H, m),5.82(1H, s), 6.65(1H, s), 6.80(1H, s), 6.86-7.06(3H, m), 7.25-7.33(1H,m), 7.54(1H, d, J=2.7 Hz), 7.68(1H, d, J=2.7 Hz). MS: 427(M+H)+ 8 H

H Me Me H N1: 0.96(3H, d, J=6.9 Hz), 1.09(3H, d, J=6.9 Hz),2.65-3.40(5H, m), 3.76(1H, d, J=16.5 Hz), 3.86(1H, d, J=16.5 Hz),3.90-4.05(1H, m), 5.71(1H, s), 6.67(1H, s), 6.86(1H, s), 7.16-7.38(5H,m), 7.54(1H, d, J=3.3 Hz), 7.66(1H, d, J=3.3 Hz). MS: 397(M+H)+. 9 2-Me

H Me Me H N1: 0.95(3H, d, J=6.3 Hz), 1.02(3H, d, J=6.3 Hz), 2.34(3H, s),2.65-3.25(5H, m), 3.75(1H, d, J=16.5 Hz), 3.88(1H, d, J=16.5 Hz),3.95-4.05(1H, m), 5.65(1H, s), 6.64(1H, s), 6.83(1H, s), 6.96-7.24(4H,m), 7.52(1H, d, J=3.3 Hz), 7.65(1H, d, J=3.3 Hz). MS: 411(M+H)+ 102-OCF3

H Me Me H N1: 1.00(3H, d, J=6.9 Hz), 1.04(3H, d, J=6.9 Hz),2.70-3.25(5H, m), 3.77(1H, d, J=16.5 Hz), 3.88(1H, d, J=16.5 Hz),3.95-4.05(1H, m), 5.83(1H, s), 6.78(1H, s), 6.90(1H, s), 7.16-7.50(4H,m), 7.52(1H, d, J=3.3 Hz), 7.65(1H, d, J=3.3 Hz). MS: 481(M+H)+ 11 2-OMe

H Me Me H N1: 0.97(6H, d, J=6.9 Hz), 2.65-3.25(5H, m), 3.76(1H, d,J=16.0 Hz), 3.79(3H, s), 3.83(1H, d, J=16.0 Hz), 3.91-4.02(1H, m),5.82(1H, s), 6.62(1H, s), 6.77(1H, s), 6.84-7.04(3H, m), 7.14-7.31(3H,m), 7.66(1H, dt, J=7.5&1.8 Hz), 8.44-8.50(1H, m). MS: 421(M+H)+ 12 2-OMe

H Me Me H N1: 0.90-3.50(15H, m), 3.74(1H, d, J=16.0 Hz), 3.83(3H, s),3.84(1H, d, J=16.0 Hz), 3.90-4.04(1H, m), 5.80(1H, s), 6.65(1H, s),6.79(1H, s), 6.84-7.06(3H, m), 7.23-7.32(1H, m). MS: 427(M+H)+ 13 2-OMe

H H H H N1: 2.50-3.95(10H, m), 3.77(3H, s), 6.06(1H, br s),6.76-7.05(5H, m), 7.28(1H, t, J=6.9 Hz), 7.55(1H, m), 7.68(1H, m). MS:399(M+H)+ 14 2-OMe

H Et Et H N1: 7.30-7.40(1H, m), 6.9-7.1(3H, m), 6.4-6.5(1H, brs),6.09-6.18(1H, brs), 3.90-4.22(3H, m), 3.89(3H, s), 3.15-3.40(2H, m),2.34(3H, s), 2.08-2.28(1H, m), 1.50-1.75(2H, m), 1.12-1.30(1H, m),0.86(3H, t, J=7.5), 0.15(3H, t, J=7.5). MS: 358(M 15 2-OMe

H Et Et H N1: 7.26-7.38(1H, m), 6.88-7.04(3H, m), 6.79(1H, s), 6.45(1H,s), 5.57(1H, s), 4.45-4.70(2H, m), 4.25-4.35(1H, brs), 3.90-4.00(2H, m),3.81(3H, s), 2.98-3.10(1H, m), 2.05-2.20(2H, m), 1.50-1.65(1H, m),1.00-1.20(1H, m), 0.78(3H, t, J=7.5),

Example 16 Evaluation of the Sugar Transporting Capacity

1. Preparation of Adipose Cells of Rats:

After the decapitation and venesection of 6 male Wistar rats (bodyweight: 150 to 200 g), an incision was made in the abdomen of each ratto extract 6 g in total of epididymal adipose tissues. The tissues werefinely cut into 2 mm×2 mm pieces in 6 ml of KRH (Krebs-Ringer Hepes,composition: 130 mM of sodium chloride, 4.7 mM of potassium chloride,1.2 mM of potassium dihydrogenphosphate, 1.2 mM of magnesium sulfate, 1mM of calcium chloride and 25 mM of Hepes, pH=7.6) containing 5% of BSA(bovine serum albumin). 24 mg of collagenase (type I) was added theretoand the digestion treatment was conducted for about 40 minutes to obtainabout 6 ml of isolated adipose cells. The collagenase was removed by thebuffer exchange. 2% BSA/KRH solution was added to the residue for there-suspension to obtain 45 ml of an adipose cell suspension.

2. Evaluation of the Sugar Transporting Capacity:

The sugar transporting capacity of the compound of the present inventionwas evaluated with reference to a method described in a literature[Annual Review of Biochemistry, Vol. 55, p. 1059 (1986)]. In the test,200 μL of the adipose cell suspension was poured in each polystyrenetest tube, 100 μL of the solution of the test substance (by dilution of10 mg/mL dimethyl sulfoxide solution with KRH) was added thereto, andthe obtained mixture was shaken and then cultured at 37° C. for 30minutes.

The sugar transporting capacity was evaluated by measuring the quantityof 2-[¹⁴C(U)]-deoxy-D-glucose incorporated per a unit time. Namely,2-[¹⁴C(U)]-deoxy-D-glucose was added to the adipose cell suspensionafter the pre-culture (the final concentration: 0.5 μCi/sample). 5minutes later, cytochalasin B (final concentration: 10 μM) was added tothe mixture to terminate the sugar transportation. After forming adinonyl phthalate layer, the obtained mixture was centrifuged toseparate the adipose cells from the buffer. The quantity of2-[¹⁴C(U)]-deoxy-D-glucose contained in the adipose cell layer wasdetermined with a liquid scintillation counter to determine the quantityof the incorporated sugar. In this evaluation system, when insulin (100nM) having the effect of increasing the sugar-transporting capacity wasused, the effect was about 7 times as high as that obtained in theinsulin-free control group.

The results of the evaluation of the sugar-transporting capacityobtained by using the compounds of the present invention are shown inTable 2. The sugar-transporting capacity in Table 2 was determined interms of the concentration (EC₅₀: μg/mL) of a test compound, having areinforcing effect corresponding to 50% on the basis of the reinforcingeffect of insulin (100 nM). (The symbols in Table 2 are as follows: No:Example No., and A: sugar-transporting capacity.)

TABLE 2 No. A 3 6.0 7 0.06 8 0.31 9 0.15 10 0.2 11 <0.1

1. A fused polycyclic compound of formula (I) or a pharmaceuticallyacceptable salt thereof:

wherein: A represents an aromatic cyclic group, heterocyclic group oraliphatic cyclic group; R¹, R² and R³ may be same or different from eachother and each independently represent a hydrogen atom, halogen atom,hydroxyl group, mercapto group, alkoxy group, alkylthio group,alkylsulfonyl group, acyl group, acyloxy group, amino group, alkylaminogroup, carboxyl group, alkoxycarbonyl group, carbamoyl group, nitrogroup, cyano group, trifluoromethyl group, alkyl group which may have asubstituent(s), alkenyl group which may have a substituent(s), alkynylgroup which may have a substituent(s), aryl group which may have asubstituent(s), heteroaryl group which may have a substituent(s),benzyloxy group which may have a substituent(s), aryloxy group which mayhave a substituent(s), heteroaryloxy group which may have asubstituent(s), arylamino group which may have a substituent(s),arylvinyl group which may have a substituent(s) or arylethynyl groupwhich may have a substituent(s); —Z— represents —O—, —NH—, —NR⁶—, —S—,—SO—, —SO₂—, —CH₂—, —CR⁴R⁵— or —CO—, wherein R⁶ represents a lower alkylgroup which may have a substituent(s), acyl group which may have asubstituent(s), alkoxycarbonyl group which may have a substituent(s),carbamoyl group which may have a substituent(s) or sulfonyl group whichmay have a substituent(s), R⁴ and R⁵ may be same or different from eachother and each independently represent a hydrogen atom, halogen atom,hydroxyl group, alkyl group, mercapto group, alkoxy group, alkylthiogroup, alkylsulfonyl group, acyl group, acyloxy group, amino group,alkylamino group, carboxyl group, alkoxycarbonyl group, carbamoyl group,nitro group, cyano group or trifluoromethyl group; —X— represents —NH—or —NR⁶—; —W— represents —NR⁹—, —O— or —CR⁷R⁸—, wherein R⁹ represents ahydrogen atom, lower alkyl group which may have a substituent(s) or arylgroup which may have a substituent(s), R⁷ and R⁸ may be same ordifferent from each other and each independently represent a hydrogenatom, halogen atom, hydroxyl group, alkyl group, mercapto group, alkoxygroup, alkylthio group, alkylsulfonyl group, acyl group, acyloxy group,amino group, alkylamino group, carboxyl group, alkoxycarbonyl group,carbamoyl group, nitro group, cyano group or trifluoromethyl group; Yrepresents a lower alkyl group which may have a substituent(s), acylgroup which may have a substituent(s), alkoxycarbonyl group which mayhave a substituent(s), carbamoyl group which may have a substituent(s)or sulfonyl group which may have a substituent(s); R¹⁰, R¹¹, R¹² and R¹³may be same or different from each other and each independentlyrepresent a hydrogen atom, halogen atom, lower alkyl group which mayhave a substituent(s), lower alkenyl group which may have asubstituent(s), lower alkynyl group which may have a substituent(s),aryl group which may have a substituent(s), heteroaryl group which mayhave a substituent(s), carboxyl group, alkoxycarbonyl group, carbamoylgroup or cyano group; and a, b and c represent a position of a carbonatom, respectively; with the proviso that (i) the above substituent(s)is selected from the group consisting of a halogen atom, hydroxyl group,alkyl group, mercapto group, alkoxy group, alkylthio group,alkylsulfonyl group, acyl group, acyloxy group, amino group, alkylaminogroup, carboxyl group, alkoxycarbonyl group, carbamoyl group, nitrogroup, cyano group, trifluoromethyl group, aryl group and heteroarylgroup; and (ii) two or more of R¹⁰, R¹¹, R¹² and R¹³ do not form a ringtogether.
 2. The fused polycyclic compound or pharmaceuticallyacceptable salt thereof according to claim 1, wherein A represents anaromatic cyclic group or heterocyclic group; —Z— represents —CH₂— or—CR⁴R⁵—; —W— represents —NR⁹—; Y represents an acyl group which may havea substituent(s), alkoxycarbonyl group which may have a substituent(s)or carbamoyl group which may have a substituent(s); either one or bothof R¹⁰ and R¹¹ is a hydrogen atom; and either one or both of R¹² and R¹³is a hydrogen atom.
 3. The fused polycyclic compound or pharmaceuticallyacceptable salt thereof according to claim 2, wherein Y is an acyl groupwhich may have a substituent(s) and is represented by formula (II):

wherein two carbon atoms in T may have a double bond or triple bond,some of the carbon atom(s) in the group may be substituted with anoxygen, sulfur or nitrogen atom, and T represents an alkylene grouphaving 1 to 7 carbon atoms; and C represents an aromatic cyclic group orheterocyclic group which may have a substituent(s).
 4. The fusedpolycyclic compound or pharmaceutically acceptable salt thereofaccording to claim 2, wherein Y is an acyl group which may have asubstituent(s) and is represented by formula (II):

wherein C represents a furyl group which may have a substituent(s),thienyl group which may have a substituent(s), oxazolyl group which mayhave a substituent(s), isoxazolyl group which may have a substituent(s),thiazolyl group which may have a substituent(s), oxadiazolyl group whichmay have a substituent(s), thiadiazolyl group which may have asubstituent(s), pyridyl group which may have a substituent(s), piperidylgroup which may have a substituent(s), pyridonyl group which may have asubstituent(s), pyridazinyl group which may have a substituent(s),pyrimidinyl group which may have a substituent(s), imidazolyl groupwhich may have a substituent(s), or 4-oxothiazolidine-2-thionyl groupwhich may have a substituent(s); and -T- represents —CH₂— or —CH₂CH₂—.5. The fused polycyclic compound or pharmaceutically acceptable saltthereof according to claim 4, wherein C represents a furyl group,thienyl group, oxazolyl group, isoxazolyl group, thiazolyl group,oxadiazolyl group, pyridyl group, piperidyl group, pyridazinyl group, orpyrimidinyl group.
 6. The fused polycyclic compound or pharmaceuticallyacceptable salt thereof according to claim 2, wherein Y represents anunsubstituted acyl group or an acyl group which has an alkyl group(s)with 1 to 6 carbon atoms having a hydroxyl group as a substituent. 7.The fused polycyclic compound or pharmaceutically acceptable saltthereof according to claim 2, wherein A is a phenyl group; —X—represents —NH— or —NMe-; W is —NH—; both R¹⁰ and R¹³ are hydrogenatoms; and R¹¹ and R¹² may be same or different from each other and eachindependently represent a hydrogen atom, lower alkyl group which mayhave a substituent(s), lower alkenyl group which may have asubstituent(s), or lower alkynyl group which may have a substituent(s).8. The fused polycyclic compound or pharmaceutically acceptable saltthereof according to claim 2, wherein all of R¹, R² and R³ are hydrogenatoms, or two of R¹, R² and R³ are hydrogen atoms and one of R¹, R² andR³ is an alkoxy group, alkylthio group, alkylsulfonyl group, acyl group,acyloxy group, amino group, alkylamino group, alkoxycarbonyl group,carbamoyl group, trifluoromethyl group, alkyl group which may have asubstituent(s), alkenyl group which may have a substituent(s), oralkynyl group which may have a substituent(s).
 9. The fused polycycliccompound or pharmaceutically acceptable salt thereof according to claim8, wherein all of R¹, R² and R³ are hydrogen atoms, or two in R¹, R² andR³ are hydrogen atoms and one of R¹, R² and R³ is an alkoxy group having1 to 18 carbon atoms, alkylthio group having 1 to 12 carbon atoms,alkylsulfonyl group having 1 to 12 carbon atoms, trifluoromethyl group,or alkyl group having 1 to 18 carbon atoms.
 10. The fused polycycliccompound or pharmaceutically acceptable salt thereof according to claim7, wherein R¹¹ and R¹² may be same or different from each other and eachindependently represent a lower alkyl group which may have asubstituent(s), lower alkenyl group which may have a substituent(s), orlower alkynyl group which may have a substituent(s).
 11. The fusedpolycyclic compound or pharmaceutically acceptable salt thereofaccording to claim 10, wherein R¹¹ and R¹² may be same or different fromeach other and each independently represent a lower alkyl group whichmay have a substituent(s).
 12. A pharmaceutical composition, whichcomprises a fused polycyclic compound or pharmaceutically acceptablesalt thereof according to claim 1 and one or more pharmaceuticallyacceptable excipients.
 13. A pharmaceutical composition, which comprisesa fused polycyclic compound or pharmaceutically acceptable salt thereofaccording to claim 2 and one or more pharmaceutically acceptableexcipients.
 14. A pharmaceutical composition, which comprises a fusedpolycyclic compound or pharmaceutically acceptable salt thereofaccording to claim 3 and one or more pharmaceutically acceptableexcipients.
 15. A pharmaceutical composition, which comprises a fusedpolycyclic compound or pharmaceutically acceptable salt thereofaccording to claim 4 and one or more pharmaceutically acceptableexcipients.
 16. A pharmaceutical composition, which comprises a fusedpolycyclic compound or pharmaceutically acceptable salt thereofaccording to claim 5 and one or more pharmaceutically acceptableexcipients.
 17. A pharmaceutical composition, which comprises a fusedpolycyclic compound or pharmaceutically acceptable salt thereofaccording to claim 6 and one or more pharmaceutically acceptableexcipients.
 18. A pharmaceutical composition, which comprises a fusedpolycyclic compound or pharmaceutically acceptable salt thereofaccording to claim 7 and one or more pharmaceutically acceptableexcipients.
 19. A pharmaceutical composition, which comprises a fusedpolycyclic compound or pharmaceutically acceptable salt thereofaccording to claim 8 and one or more pharmaceutically acceptableexcipients.
 20. A pharmaceutical composition, which comprises a fusedpolycyclic compound or pharmaceutically acceptable salt thereofaccording to claim 9 and one or more pharmaceutically acceptableexcipients.